Randomized, placebo-controlled phase II trial of heat-killedMycobacterium vaccae(Longcom batch) formulated as an oral pill (V7)

Abstract

One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 μg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.4%) cases distributed at 5:4:13 and 3:2:16 ratios, respectively. Both arms received conventional TB drugs administered under directly observed therapy. The average weight gain in V7 arm was modest, but statistically significant (0.6 kg; p = 0.004), while placebo patients lost 0.1 kg (p = 0.77). Except defervescence and increased lymphocyte percentage, other secondary endpoints such as erythrocyte sedimentation rate (ESR), leukocyte counts and hemoglobin content were not significantly affected. In control patients only one secondary endpoint, ESR, has improved. After one month mycobacterial clearance in sputum smears was observed in 31.8% (p = 0.03) and 9.5% (p = 0.83) of patients on V7 and placebo. However, the difference between outcomes in two arms was below significance threshold (p = 0.07). Thus, larger population of patients with prolonged follow-up is required to support these preliminary findings.

Randomized, Placebo-Controlled Phase II Trial of Heat-Killed Mycobacterium Vaccae (Immodulon Batch) Formulated as an Oral Pill (V7)

“…Alternatively, other sources of M. vaccae need to be evaluated to establish optimally effective formulation. A manuscript describing a clinical trial of V7 formulation based on the Chinese version of M. vaccae is now published online ahead of print [29].…”

Efficacy of Mycobacterium vaccae immunotherapy for patients with tuberculosis: A systematic review and meta-analysis

“…Thus, 13 studies were included in the meta-analysis. 7,11,12,[15][16][17][18][19][20][21][22][23][24] A summary of the basic characteristics of the included studies is shown in Table 1. The number of patients in the studies ranged from 22 to 1337, and the mean patient age ranged from 26.4 to 44.3 y.…”

“…Of 9 studies 7,11,12,15,18,21,[22][23][24] that reported results of sputum smear clearance assessed at 1 or 2 months, all showed that patients treated with M. vaccae immunotherapy had higher odds of sputum smear conversion to negative than patients in the placebo group. Heterogeneity was present across studies, and thus a random-effects model of analysis was used (Q D 17.3, P D .028; I 2 D 53.6%).…”

“…4 M. vaccae is a nonpathogenic species commonly found in soil and water belonging to the same genus as M. tuberculosis that was first described in 1964 by Bonickse and Juhasz. 5 M. vaccae was first examined as a TB vaccine in the 1980s by Stanford et al 6 Since that time its safety has been documented, 7 and it has been extensively investigated as an immunotherapeutic agent for the treatment of TB and in unrelated disorders including cancer and autoimmune disease. 8,9 M. vaccae is available in injectable and oral forms.…”

Novel drugs against tuberculosis: a clinician's perspective

“…Adjunct immunotherapy, which includes host-directed therapies with immunoadjuvants [123][124][125], recombinant cytokines [126][127][128] or therapeutic vaccinations [128][129][130][131][132][133][134][135][136][137][138], should be further explored to possibly improve the treatment outcome of drug-resistant TB, especially difficult forms of MDR/XDR-TB [139].…”